Kynuramines occur endogenously via the metabolism of L-tryptophan and associated indoleamines. However, their pharmacological and potential physiological actions remain for elucidation. Structurally, kynuramine resembles both tryptamine and phenylethylamine and actions at indoleamine and adrenergic receptors have been found in vitro. The present objective is to evaluate the cardiovascular actions of several kynuramines and an amino acid precursor, L-kynurenine. Ring hydroxylation and N-methylation of kynuramine will permit structure activity studies, while L-kynurenine will test for endogenous kynuramine production at both central and peripheral sites. Acute experiments (kynuramines and L-kynurenine) and chronic experiments (L-kynurenine) using pithed and anesthetized rats are designed to characterize the pharmacological effects of the compounds on heart rate and blood pressure. The tests include studies on specificity by using selected agonist and antagonist drugs, effects on sympathetic nerve stimulation, the involvement of endogenous norepinephrine release and the role of amine oxidases in the metabolism of the compounds. Biochemical studies using isolated atria and tritium-labelled norepinephrine will determine the mechanism whereby kynuramines evoke amine release and will investigate interactions with amine oxidase, uptake 1, uptake 2 and presynaptic receptors on atrial sympathetic nerves. Central actions will be investigated following intraventricular administration including the influence of the kynuramines on the cardiovascular responses to posterior hypothalamic stimulation. Radio-ligand receptor binding studies will be done on brain membranes in vitro to determine affinities of the kynuramines for serotonin, adrenergic and dopaminergic receptors. In addition, possible changes in receptor numbers and/or affinities will be looked for in rats treated chronically with L-kynurenine. Finally, the isolated perfused rat brain will be utilized to test for effects on brain vasculature and to determine whether kynuramines pass the blood brain barrier. The proposed pharmacological characterization may serve to endorse the hypothesis that kynuramines and L-kynurenine may act as endogenous physiological and/or pathological regulators of central and peripheral autonomic control to the cardiovascular system.